KR950014227B1 - Method for preparing N, N'-disubstituted urea - Google Patents

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Description

Method for preparing N, N'-disubstituted urea

The present invention relates to a method for producing an N, N'-disubstituted urea represented by the following general formula (I).

Wherein Ar is an unsubstituted aromatic or aromatic group substituted with halogen, C _1-4 alkyl or C _1-4 alkoxy.

N, N'-disubstituted urea is a useful material used as a raw material of pesticides and pharmaceuticals, and there has been a continuous research to manufacture them conveniently and economically.

For example, Japanese Patent Laid-Open No. 53-41123 and Japanese Patent Laid-Open No. 58-144363 disclose a method of producing N, N'-disubstituted urea by reacting an amine with carbon monoxide and oxygen at high temperature and high pressure. However, the method has two drawbacks of carbon monoxide and oxygen, so it is difficult to control the partial pressure of the two gases in the continuous reaction, and there is a disadvantage of explosion risk since oxygen is used. In addition, Japanese Patent Application Laid-Open No. 62-59253 discloses a process for preparing N, N'-disubstituted urea by reacting an amine with carbon monoxide and nitro compounds, in which rhodium (Rh) and rutheum (Ru), etc. Expensive catalysts must be used, high temperatures of 160 ° C and sufficient reaction time are required to obtain the desired yields and selectivities, as well as the resulting N, N'-disubstituted urea properties are not clean and the catalysts are located near the reaction temperature. There was a drawback of deactivation of the catalyst due to heat instability.

In order to solve the above disadvantages, U. S. Patent No. 5,091, 571 discloses an aromatic mononitro compound, an aromatic primary amine and carbon monoxide, and a palladium compound, which is a main catalyst composed of a monodentate having only one non-covalent electron pair as a ligand. A method for synthesizing N, N'-disubstituted urea by reacting in the presence of an ammonium salt or a phosphonium salt containing a halogen element as a catalyst has been proposed.

The present inventors earnestly researched to develop a simpler and more economical method further from the existing technology, and as a result, the preparation of N, N'-disubstituted urea represented by the general formula (I) using a paramal compound as a catalyst By using a bidentate ligand having two non-covalent electron pairs as a ligand, the yield of N, N'-disubstituted urea can be maximized and the reaction time can be dramatically shortened, compared to the aromatic mononitro compound. The present invention was completed by reducing the reaction amount of a relatively expensive aromatic primary amine to improve economics.

That is, the present invention reacts an aromatic mononitro compound with an aromatic primary amine and carbon monoxide in the presence of an ammonium salt or a phosphonium salt containing palladium compound 주 as a main catalyst and a halogen element as a promoter to form N in the following general formula (I) , N'- di prepared as in a substituted urea, is displayed as the Palazzo placing compound by the general formula L ₂ PdX _2, wherein X is a _{halogen, -NO 2, -OCOCH 3, -OCOCF} 3, L is a ligand general Formula Ph ₂ P (CH ₂ ) n PPh ₂ wherein Ph is phenyl and n is an integer of 2 to 5 to provide a method for producing N, N′-disubstituted urea.

Wherein Ar represents an aromatic group which is unsubstituted aromatic or substituted by halogen, C _1-4 alkyl or C _1-4 alkoxy.

The present invention will be described in detail as follows.

Aromatic mononitro compounds used in the present invention include nitrobenzene, nitronaphthalenes, nitroanthracenes, nitrobiphenyls, and the like. Nitrobenzene, o-, m-, p-chloronitrobenzene, 1 -Bromo-4-nitrobenzene, 2-chloro-6-nitrotoluene, 4-chloro-3-nitrotoluene, 1,4-dichloro-2-nitrobenzene, 3,4-dichloro-1-nitrobenzene, α -Chloro-n-nitrotoluene, 1,2,4-trichloro-5-nitrobenzene and the like.

In addition, the aromatic primary amines used in the present invention include aniline, aminonaphthalenes, aminoanthracenes, aminobinungnils and the like, and specific compounds include aniline, o-, m-, p-toluidine, o-, m-, p-chloroaniline, α-naphthalamine, 2-methyl-1-aminonaphthalene, aminotoluene and the like.

Since the aromatic primary amine can be used as a solvent to dissolve not only the reactants but also the catalyst components in the reaction of the present invention, it is usually used in excess, preferably 2 moles or more, with respect to the aromatic mononitro compound. Thus, the excessive use of the aromatic primary amine can prevent inactivation of the catalyst and facilitate catalyst recovery.

The palladium compound used as a main catalyst in the present invention contains a palladium element in a divalent state, and is a palladium complex compound represented by the general formula PdX ₂ L ₂ . Wherein X is a _{halogen, -NO 3, -OCOCH 3, -OCOCF} 3, L represents a ligand. In particular, the ligand used in the present invention is a bidentate ligand having two non-covalent electron pairs, and when the palladium compound catalyst is used in the form of PdX ₂ , the ligand is used to not only enhance the activity of the catalyst but also prevent inactivation of the catalyst. do. The bodydentate ligands of the present invention are represented by the general formula Ph ₂ P (CH ₁ ) nPPh ₂ , where Ph is phenol and n is an integer from 2 to 5, specifically 1,2-bis (diphenyl phosph) Pino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane and 1,5-bis (diphenylphosphino) heptane.

The reaction for synthesizing the N, N'-disubstituted urea of the general formula (I) according to the present invention can be represented by the following reaction formula (1) and (2).

ArNO ₂ + ArNH ₂ + 3CO → ArNHCONHAr + 2CO ₂ (1)

ArNO ₁ + 5ArNH ₂ + 3CO → ArNHCONHAr + 2ArNHCONHAr + 2CO ₂ (2)

In the above formulas, Ar is the same as described above.

The use of the bidentate trigand as the ligand of the palladium compound as the main catalyst makes the reaction formula (1) superior to the reaction formula (2), thus reducing the reaction amount of the aromatic primary amine compared to the case of using the monodentate ligand. do.

The palladium complex compound used as the main catalyst is preferably used in an amount of 1/10 to 1/3000 mole times with respect to the aromatic mononitro compound. In addition, the ligand is preferably used in an amount of at least twice the number of moles used catalyst.

On the other hand, a compound comprising a halogen element used as a co-catalyst in the process of the present invention has the general formula ^{_{[R 4, N -] X}} - represented by X ^{+ -} ammonium salts with the formula [R _4, P] is represented by There is a phosphonium salt. R is hydrogen, an aliphatic group, an alicyclic group, an aromatic group or an aromatic aliphatic group, and X is a halogen element.

Specifically, as the ammonium salt, tetraethyl ammonium chloride, tetramethyl ammonium chloride, tetrabutyl ammonium chloride, tetraethyl ammonium bromide, tetrabutyl ammonium bromide, tetrabutyl ammonium bromide, tetraethyl ammonium iodine, tetramethyl Ammonium iodine, tetrabutyl ammonium iodine or trimethylbenzyl ammonium chloride, and the like, and phosphonium salts include tetrabutyl phosphonium bromide, pttramethyl phosphonium bromide, tetraethyl phosphonium bromide, and tetraethyl phosphony Um chloride, tetramethyl phosphonium chloride, tetrabutyl phosphonium bromide, tetramethyl phosphonium iodine, pttrabutyl phosphonium iodine or tetraethyl phosphonium iodine and the like.

The ammonium salt or phosphonium um used as a cocatalyst is used in an amount of 1 to 20 mol times with respect to the palladium compound. When an amount of 1 mol or less is used, the reaction does not proceed sufficiently, and an amount of 20 mol times or more is economical. It is unreasonable.

The amount of catalyst met ligand based on the palladium compound is completely dissolved in the reaction and is adjusted in the liquid phase so that the solubility of each component, the reaction temperature, the amount of aromatic primary amine, the type and amount of the solvent are adjusted according to the reaction conditions. It is desirable to give.

In the reaction according to the present invention, a solvent may or may not be used as necessary, but a non-polar solvent having a low solubility of N, N'-disubstituted urea of general formula (I) is suitable. , Benzene, toluene, xylene or mixtures thereof are preferred.

The reaction proceeds in the range of 50 to 200 ° C, preferably in the range of 80 to 140 ° C, more preferably in the range of 90 to 120 ° C. If the reaction temperature is too low, the amount of the unreacted mononitro compound is increased. If the reaction temperature is too high, the catalyst is deactivated to deactivate the catalyst or decompose the catalyst.

Although the reaction pressure can be 1 atm or more, preferably 5 to 100 atm, more preferably 5 to 40 atm, the reaction is suitable. At a pressure below 5 atm, the reaction does not proceed quickly. Economics are a problem because equipment costs are high. The reaction time is preferably 10 minutes to 600 minutes, depending on the type of reactants used, reaction pressure, temperature, type of catalyst and amount used.

When the reaction is completed, the N, N'-disubstituted urea of the general formula (I) is low in solubility to precipitate as a solid, and the main catalyst and the promoter are present in the liquid phase together with the unreacted material and the solvent. The main catalyst and promoter can be recovered almost completely by separating and washing the separator. In order to purify the produced urea with high purity and to increase the recovery rate of the main catalyst and the promoter, it is necessary to wash the solid component obtained by filtration and then filter it using reduced pressure, pressure, centrifuge or the like.

Aromatic primary amines are suitable as the washing solution used in the method of the present invention, and in particular, the same amines as those used in the reaction can be used directly in the next reaction without further manipulation.

Hereinafter, the present invention will be described in detail with reference to Examples. The following examples are provided to illustrate the invention but do not limit the invention.

All reactions described in the examples were performed in batches in a 300 ml autoclave. The reaction was heated with a heater installed outside the reactor, and after the reaction was completed, it was cooled by cooling water flowing along a cooling coil installed inside the reactor. The product was prepared using t-butylbenzene as an internal standard. Analysis was performed by gas chromatography and high performance liquid chromatography. The yield of N, N'-disubstituted urea was calculated by the following formula.

(Examples 1 to 3)

27.9 g (300 mmol) of aniline in 300 ml autoclave, 0.1359 (0.601 mmol) of palladium acetate (Pd (CH ₃ COO) ₂ ), ligands of the kind and amount shown in Table 1, tetraethyl ammonium chloride (NEt ₄ Cl ) 1.8 g, t-butyl benzene (internal standard for gas chromatographic analysis) and 60 g of xylene were added. After substituting three times the gaseous part with 10 atm of carbon monoxide, the temperature was changed to 40 atm. It became. While the reactor was stirred, the temperature was raised to 120 ° C. 6.15 g (50 mmol) of nitrobenzene was added by a high pressure metering pump and reacted for a time as shown in Table 1, and then a sample was taken through a sample order valve and analyzed by gas chromatography. After the reaction was completed, the solid phase reactor was cooled to room temperature, and then gas was discharged. After the reaction was filtered under reduced pressure, the solid product was washed with aniline (18.6 g, 200 mmol) and xylene (50 g) and dried. Gas chromatography analysis showed no nitrobenzene. The reaction results are shown in Table 1.

TABLE 1

Comparative Example 1

The reaction was carried out under the same conditions as in Example except that the reaction was carried out for 2 hours without using a ligand.

Comparative Example 2

The reaction was carried out under the same conditions as in Example except that the reaction was performed for 4 hours using 3.48 mmol of trifenyl phosphite (P (OPh) ₃ ) as a ligand. As a result, the conversion of nitrobenzene was 19.0%, but N, N'-diphenyl urea was not produced.

Comparative Example 3

The reaction was carried out under the same conditions as in Example except that the reaction was carried out using 3.48 mmol of triethylphosphite (P (OEt) ₃ ) as a ligand for 4 hours. As a result, the conversion rate of nitrobenzene was 24.1%, but N, N'-diphenyl larvae were not produced.

[Comparative Example 4]

The reaction was carried out under the same conditions as in Example except that the reaction was performed for 1.5 hours using 3.48 mmol of triphenyl phosphine (PPh ₃ ) as a ligand. As a result, the conversion of nitrobenzene was 100%, and the selectivity of N, N'-diphenyl urea was 98%.

Claims (9)

An aromatic mononitro compound, an aromatic primary amine, and carbon monoxide are reacted in the presence of an ammonium salt or a phosphonium salt containing a palladium compound as a main catalyst and a halogen element as a promoter to form N, N'-di of the following general formula (I) in preparing the substituted urea is represented by the general formula L ₂ PdX ₂ as the palladium compound, in which X is _{halogen, -NO 3, -OCOCH 3, -OCOCF} 3 , and, L is the formula Ph ₂ P (CH as a ligand ₂ ) A process for producing N, N'-disubstituted urea, characterized by using nPPh ₂ , wherein Ph is phenyl and n is an integer from 2 to 5. Wherein Ar represents an unsubstituted aromatic group or an aromatic group substituted with halogen, C _1-4 alkyl or C _1-4 alkoxy. The ammonium salt of claim 1, wherein the ammonium salt comprising a halogen element is tetratormonium ammonium chloride, tetramethyl ammonium chloride, tetrabutyl ammonium chloride, tetraethyl ammonium bromide, tetratorammonium bromide, tetrabutyl ammonium. Boromid, tetramethyl ammonium iodine, detraethyl ammonium iodine, tetrabutyl ammonium iodine or trimethylbenzyl ammonium chloride. The method of claim 1, wherein the phosphonium including the halogen element is tetrabutyl phosphonium bromide, tetramethyl phosphonium bromide, tetratorethyl phosphonium bromide, tetraethyl phosphonium chloride, tetramethyl phosphonium Chloride, tetrabutyl phosphonium chloride, tetramethyl phosphonium iodine, tetrabutyl phosphonium iodine or tetraethyl phosphonium iodine. The method of claim 1 wherein said reaction is carried out in the presence of a nonpolar solvent. The method of claim 4, wherein the nonpolar solvent is benzene, toluene, xylene or mixtures thereof. The process of claim 1 wherein said reaction is carried out at 50 to 200 ° C. The method according to claim 1, wherein the aromatic primary amine is used at least 2 molar times with respect to the aromatic mononitro compound. The method according to claim 1, wherein the main catalyst is used in an amount of 1/10 to l / 3000 mole times with respect to the aromatic mononitro compound. The method of claim 1 wherein the ligand is used in an amount of at least twice the number of moles of catalyst used.